In vivo effect of pneumonia on surfactant disaturated-phosphatidylcholine kinetics in newborn infants

Bacterial pneumonia in newborns often leads to surfactant deficiency or dysfunction, as surfactant is inactivated or its production/turnover impaired. No data are available in vivo in humans on the mechanism of surfactant depletion in neonatal pneumonia. We studied the kinetics of surfactant's major component, disaturated-phosphatidylcholine (DSPC), in neonatal pneumonia, and we compared our findings with those obtained from control newborn lungs

Surfactant disaturated-phosphatidylcholine kinetics in acute respiratory distress syndrome by stable isotopes and a two compartment model

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), it is well known that only part of the lungs is aerated and surfactant function is impaired, but the extent of lung damage and changes in surfactant turnover remain unclear. The objective of the study was to evaluate surfactant disaturated-phosphatidylcholine turnover in patients with ARDS using stable isotopes. METHODS: We studied 12 patients with ARDS and 7 subjects with normal lungs. After the tracheal instillation of a trace dose of (13)C-dipalmitoyl-phosphatidylcholine, we measured the (13)C enrichment over time of palmitate residues of disaturated-phosphatidylcholine isolated from tracheal aspirates. Data were interpreted using a model with two compartments, alveoli and lung tissue, and kinetic parameters were derived assuming that, in controls, alveolar macrophages may degrade between 5 and 50% of disaturated-phosphatidylcholine, the rest being lost from tissue. In ARDS we assumed that 5–100% of disaturated-phosphatidylcholine is degraded in the alveolar space, due to release of hydrolytic enzymes. Some of the kinetic parameters were uniquely determined, while others were identified as lower and upper bounds. RESULTS: In ARDS, the alveolar pool of disaturated-phosphatidylcholine was significantly lower than in controls (0.16 ± 0.04 vs. 1.31 ± 0.40 mg/kg, p < 0.05). Fluxes between tissue and alveoli and de novo synthesis of disaturated-phosphatidylcholine were also significantly lower, while mean resident time in lung tissue was significantly higher in ARDS than in controls. Recycling was 16.2 ± 3.5 in ARDS and 31.9 ± 7.3 in controls (p = 0.08). CONCLUSION: In ARDS the alveolar pool of surfactant is reduced and disaturated-phosphatidylcholine turnover is altered

Surfactant disaturated-phosphatidylcholine kinetics in acute respiratory distress syndrome by stable isotopes and a two compartment model

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), it is well known that only part of the lungs is aerated and surfactant function is impaired, but the extent of lung damage and changes in surfactant turnover remain unclear. The objective of the study was to evaluate surfactant disaturated-phosphatidylcholine turnover in patients with ARDS using stable isotopes. METHODS: We studied 12 patients with ARDS and 7 subjects with normal lungs. After the tracheal instillation of a trace dose of (13)C-dipalmitoyl-phosphatidylcholine, we measured the (13)C enrichment over time of palmitate residues of disaturated-phosphatidylcholine isolated from tracheal aspirates. Data were interpreted using a model with two compartments, alveoli and lung tissue, and kinetic parameters were derived assuming that, in controls, alveolar macrophages may degrade between 5 and 50% of disaturated-phosphatidylcholine, the rest being lost from tissue. In ARDS we assumed that 5–100% of disaturated-phosphatidylcholine is degraded in the alveolar space, due to release of hydrolytic enzymes. Some of the kinetic parameters were uniquely determined, while others were identified as lower and upper bounds. RESULTS: In ARDS, the alveolar pool of disaturated-phosphatidylcholine was significantly lower than in controls (0.16 ± 0.04 vs. 1.31 ± 0.40 mg/kg, p < 0.05). Fluxes between tissue and alveoli and de novo synthesis of disaturated-phosphatidylcholine were also significantly lower, while mean resident time in lung tissue was significantly higher in ARDS than in controls. Recycling was 16.2 ± 3.5 in ARDS and 31.9 ± 7.3 in controls (p = 0.08). CONCLUSION: In ARDS the alveolar pool of surfactant is reduced and disaturated-phosphatidylcholine turnover is altered

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

Because minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmonary dysplasia, using stable isotopes, radioactive isotopes, and direct pool size measurements. Eight ventilated premature baboons received (2)H-DPPC (dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive (14)C-DPPC with a treatment dose of surfactant on d 8. After 14 d, lung pool sizes of saturated phosphatidylcholine were measured. Half-life of (2)H-DPPC (d 5) in tracheal aspirates was 28 +/- 4 h (mean +/- SEM). Half-life of radioactive DPPC (d 8) was 35 +/- 4 h. Saturated phosphatidylcholine pool size measured with stable isotopes on d 5 was 129 +/- 14 micro mol/kg, and 123 +/- 11 micro mol/kg on d 14 at autopsy. Half-lives were comparable to those obtained at d 0 and d 6 in our previous baboon studies. We conclude that surfactant metabolism does not change during the early development of bronchopulmonary dysplasia, more specifically, the metabolism of exogenous surfactant on d 8 is similar to that on the day of birth. Surfactant pool size is low at birth, increases after surfactant therapy, and is kept constant during the first 2 wk of life by endogenous surfactant synthesis. Measurements with stable isotopes are comparable to measurements with radioactive tracers and measurements at autopsy

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Early inhaled budesonide for the prevention of bronchopulmonary dysplasia

BACKGROUND Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear. METHODS We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks. RESULTS A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P = 0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P = 0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P = 0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P = 0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P = 0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups. CONCLUSIONS Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality

Rejection of false saturation data in optical pulse-oximeter

The measurement of concentration of blood gases (in particular O2) is of extreme interest for the evaluation of efficiency of pulmonary gas exchange, adequacy of alveolar ventilation, mechanisms of blood-gas transport and tissue oxygenation. Invasive techniques, although still common in many clinical situations, present the limit to be necessary not continuous, time-delayed (typically 20-30 min), painful and with an associated risk. Such limitation becomes particularly severe in critical ill patients where close and frequent (continuous) monitoring of arterial blood gases is essential. In this paper, we describe a real-time, novel measurement procedure to validate non-invasive arterial oxygen saturation (SO2) data measured by standard pulse-oxymeter. Such instrument, especially when used in intensive care units (ICU), can produce wrong data due to voluntary or involuntary motion artefacts or imperfect skin-sensor contact. We have monitored (sampling frequency: 1 Hz) in 14 preterm subjects and used the heart rate (HR) signal provided by the ECG (II-lead) and the same quantity provided by the SO2 sensor (SHR); such data have been used to validate the SO2 data. A dedicated algorithm has been developed in order to provided “most-probable” values in case of single or few not validated SO2 data. Results show that less than 10% of the arterial oxygen saturation data are not validated, which means, in our case, 25 hours of data (out of 250 hours observed) are not validated. With the provided algorithm the still not validated data are reduced to less than 5%

Neonatal outcome of small for gestational age preterm infants

Abstract Small for gestational age (SGA) preterm neonates (birth weight < -2 SDS) are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA (AGA) neonates. It is unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality. We analyzed data from 515 neonates born <30 weeks GA, 98(19%) were SGA. SGA were compared to AGA by univariate analysis and logistic regression analysis (LRA). Significant variables at univariate analysis were IUGR (67 vs 7%, p = 0.000), chorioamnionitis (1 vs 13%, p = 0.017), pre-eclampsia (62 vs 18%, p = 0.000), surfactant retreatment (47 vs 25%, p = 0.000), BPD (32 vs 20%, p = 0.015), death (30 vs 12%, p = 0.000), SatO2/FiO2 on day 3 (376 vs 433, p = 0.013), and SatO2/FiO2 ratio on day 28 (400 vs 448, p = 0.000). LRA found the following associations: regarding mortality, a decreased Sat/FiO2 ratio on day 3 (OR 1.99, 95% CI 1.26-3.16, p = 0.003); regarding BPD, surfactant retreatment (3.70, 2.11-6.49, p = 0.000), being SGA (2.69, 1.36-5.36, p = 0.005), decreasing GA (1.05, 1.03-1.08, p = 0.000), decreasing SatO2/FiO2 ratio on day 3 (1.25, 1.11-1.40, p = 0.000); and regarding severe RDS, pre-eclampsia (2.68, 1.58-4.55, p = 0.000) and decreasing GA (1.06, 1.04-1.08, p = 0.000). CONCLUSIONS: In our cohort of preterm infants, being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS due to multiple pathophysiologic mechanisms. What is Known: • Small for gestational age preterm neonates are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA neonates. • It is still unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality. What is New: • In our cohort of 515 preterm infants (19% SGA), being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS. • These results may be explained by the heterogeneity of mechanisms leading to SGA condition and by multiple mechanisms involving lung growth impairment and other factors

Refining the Definition of BPD: Characterization of Intercurrent Episodes

Background: The main definitions of bronchopulmonary dysplasia (BPD), proposed by Jobe-Bancalari, Shennan et al., and Walsh et al., focus on oxygen (O2)-need and ventilatory support for the first weeks of life and at 36 weeks of post-menstrual age (PMA). Oxygen need at 36 weeks of PMA is sometimes due to intercurrent episodes (IEs) other than BPD. The aim of this retrospective study was to characterize IEs and determine their impact on BPD in preterm infants born at Methods: O2-dependence for > 28 days and at 36 weeks of PMA (±10 days) was analyzed. We classified each infant according to the three BPD definitions. Patients requiring O2 or ventilator support at 36 weeks of PMA, with no need for O2 in the first 28 days of life, were qualified for having IEs if their O2/ventilator dependence (at 36 weeks) had a limited duration and/or could be ascribed to a known condition. Then, the contribution of IEs to the BPD rate was evaluated.Results: Out of 1,210 patients, the BPD infants were 431 (35.6%), 169 (14.0%), and 186 (15.4%) according to Jobe-Bancalari, Shennan et al., and Walsh et al., respectively. Twenty-eight patients had IEs (16.6% of those on O2 at 36 weeks of PMA) indicating a mild BPD overestimation (P=0.065).Conclusion: We proposed a definition of IEs and found that IEs could lead to a potential BPD overestimation. Further research is needed to find out if patients with IE, similarly to infants with BPD, are prone to childhood complications and need preventive measures